Quesne shot a six-under 65 to move a stroke ahead of England's Danny Willett. Paul Lawrie of Scotland moved into third ahead of David Howell, also of England.
"I took a lot of pleasure from how I played today," Quesne told the European Tour's website.
"I hit so many good shots; I managed to stay calm and I holed a lot of putts.
"My final round in Andalucia was the best of my career, because it was under a lot of pressure. But today was probably my second best, because the conditions were very tough and I hardly missed a shot. So I'm very happy."
Lawrie, who won last week's Johnnie Walker Championship at Gleneagles, hit a 66 to stay in the mix.
He said: "I played lovely again today, hit a lot of good putts - not all of them went in, but a fair few did. So I'm very happy with my day's work, despite the weather.
"A lot of guys don't like playing in the cold and the wet, but that plays into the hands of people like me who don't mind it.
"I've had a couple of decent sleeps, so I feel fine and raring to go. There's a nice, relaxed feel to this week anyway, which always helps."