CHARLOTTE, May 3, 2014 (AFP) - World number nine Mickelson, a five-time major champion, fired a nine-under par 63, one shot off the course record at Quail Hollow, to stand third on 11-under 205 after 54 holes.
"This was a really good day from start to finish," Mickelson said. "I drove the ball well, my irons were solid, my short game was on and I made a lot of putts."
Mickelson's front-nine 29 was the lowest start in tournament history.
Holmes sank a 21-foot chip shot at the 18th hole to cap a round of 66 and take the lead on 203 with Martin Flores, seeking his first PGA title, taking a bogey at 18 to stand second on 204.
"It has been clicking this week," Holmes said. "The last few weeks I have been driving the ball great. I'm hitting my irons well and putting well too."
Holmes, who had been playing on a medical exemption, won enough money last month to secure his spot on tour for the remainder of the year.
"It was nice to get that off my back," Holmes said. "I wasn't pressuring myself but it was nice to get that off my back.
"Tomorrow I'm going to go out there, try to stay pleasant, enjoy the walk and enjoy the ride as long as I can."
Holmes, who has battled back following brain surgery in 2011, birdied the par-3 second and par-5 fifth, and added birdies at seven and eight before closing the front nine with a bogey. He answered with birdies at the par-5 10th and 15th and closed the a flourish for the lead.
Holmes won his only two PGA titles at Phoenix in 2006 and 2008.
The course record of 62 was set by Rory McIlroy in 2010 and matched Friday by Zimbabwe's Brendon de Jonge, who was Mickelson's playing partner on Saturday.
Mickelson began a run of four birdies in a row at the par-4 third hole, including a 29-foot birdie putt at the par-4 fourth and a 38-foot birdie putt at the par-3 sixth.
"Capitalizing on the good shots, the iron shots, they are big momentum putts that carry on to the next holes," said Mickelson of his long birdie efforts.
"They got me ahead of the round. There are holes you can take advantage of but the other holes are tough."
The 43-year-old left-hander followed with a 13-foot eagle putt at the par-5 seventh and a two-foot birdie at the par-4 eighth on his way to a front-side 29.
A nine-foot birdie at the par-3 13th and a four-foot birdie at the par-5 15th pushed Mickelson to the top of the leaderboard while most of the overall leaders were just getting started.
Mickelson found a bunker at 18 but escaped with a three-foot par putt to finish off his best round of the year.
"To be able to salvage par was a big plus," Mickelson said. "It's going to be a good day tomorrow."
Mickelson seeks his 43rd PGA title, a win list that includes the 2004, 2006 and 2010 Masters, the 2005 PGA Championship and last year's British Open.
He will attempt to complete a career grand slam by winning next month's US Open at Pinehurst, where he managed one of his record six runner-up finishes in the event back in 1999, when Mickelson finished second to the late Payne Stewart.
Leading scores after Saturday's third round of the $6.9 million US PGA Wells Fargo Championship (USA unless noted, par-72):
203 - JB Holmes 70-67-66
204 - Martin Flores 67-68-69
205 - Phil Mickelson 67-75-63
206 - Kevin Kisner 72-66-68
207 - Jason Bohn 73-67-67, Justin Rose (ENG) 69-67-71
208 - Martin Kaymer (GER) 69-69-70
209 - Jonathan Byrd 68-71-70, Michael Thompson 71-69-69, Geoff Ogilvy (AUS) 72-67-70
210 - Rory McIlroy (NIR) 69-76-65, Mark Wilson 72-72-66, Pat Perez 73-71-66, Ernie Els (RSA) 76-67-67, Brendon de Jonge (ZIM) 80-62-68, Kevin Na 69-72-69, Zach Johnson 71-70-69, Roberto Castro 71-70-69, Jim Furyk 72-69-69, Charles Howell 69-71-70, Angel Cabrera (ARG) 66-69-75
211 - Gary Woodland 71-72-68, Wes Roach 71-71-69, John Merrick 71-70-70, Derek Ernst 73-68-70, Webb Simpson 68-73-70, Robert Streb 71-69-71