The 21-year-old Frenchman, who turned pro last year, came under attack from Aurelien Paret-Peintre (AG2R Citroën) on the uphill run to Vence during the closing third stage, with Paret-Peintre going on to take the stage win by five seconds.
Vauquelin took third place from the select chase group, with his 23-second GC lead over Paret-Peintre before the stage enough to see him hang on to take the yellow jersey by seven seconds.
Stage 2 winner Mattias Skjelmose (Trek-Segafredo) was second on the day and finished fifth overall, while Neilson Powless (EF Education-EasyPost) rounded out the final GC podium 10 seconds behind Vauquelin.
Paret-Peintre went solo for the stage win in Vence (Image credit: Luc ClaessenGetty Images)
The racing got underway early on the final of three stages, with the first kilometres seeing the riders take on the Col d'Eze. David Gaudu (Groupama-FDJ) was among the early attackers along with Paret-Peintre, Hugh Carthy (EF Education-EasyPost), Romain Bardet (Team DSM), among others.
Vauquelin's Arkéa-Samsic squad worked with Lotto-Dstny to shut the move down quickly, however, before Romain Grégoire (Groupama-FDJ) and Jonathan Caicedo (EF Education-EasyPost) formed the day's break on the next climb of the Col de Châteauneuf.
Neo-pro Grégoire put in an impressive ride to distance Caicedo and go solo at the front before a high pace put on by Trek-Segafredo and EF saw him caught a full 40km before the end of the 132km stage.
At that point, with no major hills left aside from the 4.2km, 4.5% Montée de la Sine, it was all about that last ascent before a 6km flat run to the finish in Vence.
It was there where Paret-Peintre decided to make his move, getting separation from the GC favourites' group and soloing to the stage win, even if he fell just short of nabbing Vauquelin's yellow jersey.
Dani Ostanek is Senior News Writer at Cyclingnews, joining in 2017 as a freelance contributor and later being hired full-time. Before joining the team, they had written for numerous major publications in the cycling world, including CyclingWeekly and Rouleur.
Dani has reported from the world's top races, including the Tour de France, Road World Championships, and the spring Classics. They have interviewed many of the sport's biggest stars, including Mathieu van der Poel, Demi Vollering, and Remco Evenepoel. Their favourite races are the Giro d'Italia, Strade Bianche and Paris-Roubaix.
