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France remain on course for a first Grand Slam for 10 years as they celebrated a first victory in Cardiff since 2010 with a 27-23 win.
Fly-half Romain Ntamack’s 17-point haul included a try with full-back Anthony Bouthier and second-row Paul Willemse also crossing.
Defending champions Wales responded with 18 points from Dan Biggar including a late try.
Prop Dillon Lewis also crossed for his first international try.
France overcame yellow cards for Gregory Alldritt and Mohamed Haouas and Wales will wonder about a second-half decision which could have yielded a penalty try but was not given.
It was Wales’ second defeat in three matches under Wayne Pivac and hopes of defending their title appear to have disappeared.
The loss also represented Wales’ first home Six Nations defeat for three years as France beat their opponents for only the second time in 10 games.
It proved a winning return to the Principality Stadium for Shaun Edwards who spent 12 years as Wales defence coach under Warren Gatland before linking up with France.
There was plenty of pre-match controversy with Wales prop Wyn Jones accusing France of illegal tactics at the scrum. France coach Fabien Galthie countered by describing that as a lack of respect for the nation.
Team manager Raphael Ibanez described the Welsh comments as puerile and questioned whether Wales fly-half Dan Biggar should have been playing after he failed a head injury assessment in the 24-14 defeat against Ireland.
Biggar completed all the concussion protocols with Wales saying they sought the advice of a globally renowned concussion expert to review the fly-half’s return.
Wales made two changes to their starting side with scrum-half Gareth Davies and flanker Ross Moriarty replacing Tomos Williams and Aaron Wainwright.
It enabled the home side to boast the most experienced starting side in Six Nations history with 859 caps to 234 caps for France.
Centre Virimi Vakatawa was the only fresh face in the France line-up with Gael Fickou switching to the wing.
The first scrum was always going to provoke interest because of the pre-match posturing but the second minute set-piece went off without incident although it laid the platform for France to concede a ruck offence and Biggar slotted over the penalty.
France responded within seven minutes when a normally reliable Leigh Halfpenny dropped a high Ntamack kick with Bouthier sprinting away to score. Ntamack converted.
Wales lost George North to a head injury assessment after 11 minutes following a heavy challenge by Fickou with Johnny McNicholl permanently replacing him.
Ntamack continued to drive France forward and slotted over a penalty after Lewis was guilty of a ruck transgression.
Under Edwards’ influence, France ferociously counter-rucked to put Wales under constant pressure in possession but they also pushed the offside line with one infringement resulting in a Biggar penalty.
France appeared to have responded with a brilliant second try for Fickou following a clever Ntamack chip kick but the Bouthier pass to Vakatawa was deemed forward following television replays.
That decision only delayed matters as Willemse powered over from a driving lineout as he bumped off an attempted McNicholl tackle. Ntamack converted.
Wales responded with a third Biggar penalty and the visitors’ constant offending resulted in a warning from English referee Matt Carley. Number eight Alldritt paid the price with a yellow card just before half-time.
Wales captain Alun Wyn Jones opted for a try attempt rather than kick a fourth penalty and launch a fresh attack at the start of the second-half with the extra man.
The gamble backfired as France held out to lead 17-9 at the interval as the home side botched their attacking opportunities and Wales wasted almost five minutes.
France ran down the clock after half-time and Wales managed no points with the numerical advantage before Alldritt returned.
Wales scored almost immediately when equal numbers were restored as prop Lewis dived over for his first international try. Biggar converted to reduce the deficit to one point.
All the momentum appeared to be with Wales until the classy Romain Ntamack intercepted a Tompkins pass to sprint away to score a converted try that mirrored his father Emile’s score against Wales 20 years ago.
An Ntamack penalty extended the deficit to 11 points before Willemse escaped giving away a penalty try after he knocked the ball forward. After watching television replays, Carley stuck with assistant referee Karl Dickson’s decision it was just a knock-on.
Wing Josh Adams was forced off the field with an ankle problem which forced a major backline reshuffle as fly-half Jarrod Evans came on in the centre and Tompkins switched to wing.
Prop Mohamed Haouas was yellow-carded for persistent scrummaging offences before France cleared the danger.
Biggar dived over for a converted try following clever work from new cap Will Rowlands and Aaron Wainwright to reduce the deficit to four points with five minutes remaining to set up an enthralling finale.
A tremendous Tompkins break was snuffed out by a brilliant turnover by France replacement hooker Camille Chat to break Wales hearts.
Wales: 15-Leigh Halfpenny, 14-George North, 13-Nick Tompkins, 12-Hadleigh Parkes, 11-Josh Adams, 10-Dan Biggar, 9-Gareth Davies; 1-Wyn Jones. 2-Ken Owens, 3-Dillon Lewis, 4-Jake Ball, 5-Alun Wyn Jones (captain), 6-Ross Moriarty, 7-Justin Tipuric, 8-Taulupe Faletau
Replacements: 16-Ryan Elias, 17-Rob Evans, 18-Leon Brown, 19-Will Rowlands, 20-Aaron Wainwright, 21-Tomos Williams, 22-Jarrod Evans, 23-Johnny McNicholl
France: 15-Anthony Bouthier, 14-Teddy Thomas, 13-Virimi Vakatawa, 12-Arthur Vincent, 11-Gael Fickou, 10-Romain Ntamack, 9-Antoine Dupont; 1-Cyril Baille, 2-Julien Marchand, 3-Mohamed Haouas, 4-Bernard Le Roux, 5-Paul Willemse, 6-Francois Cros, 7-Charles Ollivon (captain), 8-Gregory Alldritt
Replacements: 16-Camille Chat, 17-Jean-Baptiste Gros, 18-Demba Bamba, 19-Romain Taofifenua, 20-Dylan Cretin, 21-Baptiste Serin, 22-Mathieu Jalibert, 23-Thomas Ramos
Referee: Matthew Carley (England)
Touch judges: Wayne Barnes (England) & Karl Dickson (England)
TMO: Graham Hughes (England)
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