Garrigus fired a six-under-par 64 to move to 16-under 194, one clear of William McGirt (66) and two in front of Scott Piercy (67).
McGirt and Piercy had shared the lead overnight.
American players made up the top 10 players on the leaderboard with former major winners Retief Goosen of South Africa (63) and Fijian Vijay Singh (69) the best of the international challengers, seven shots back.
Garrigus carded four birdies and an eagle on a bogey-free day and promised to continue to attack on Sunday as he searches for his second US PGA Tour victory.
"It's foot to the floor as much as possible," he said. "I know I can't let anybody in the golf tournament and if I go out and make birdies they're not going to catch me so I'm just going to go hammering at flags and hit fairways and hopefully everything works out.
"I just like the way the course sets up. It's a hilly golf course, fitness is a big issue and I'm in really good shape right now so I'm loving where I am at."
Goosen rose 42 places into a tie for 11th with his seven-under round. Scott Stallings and Chris Kirk matched his 63 and share fourth spot with fellow American Bo Van Pelt (67) on 198.
Kirk looked set to smash the course record of 62 at the Hamilton Golf and Country Club after getting to seven under through 10 holes but he parred the last eight.
David Hearn and Graham DeLaet were the best of the locals on 208, meaning Canada's victory drought in the tournament is almost certain to be extended to 58 years.