Oberholtzer, pitching for the first time since straining a lat muscle on March 10, gave up five hits and five runs in 3 1-3 innings.
"There's two components — where's he at conditioning-wise, and where he's at from a sharpness standpoint," Astros manager A.J. Hinch said about Olberholtzer's odds of starting the season in the rotation. "But we'll get our group together and figure out what's next."
George Springer robbed Colabello of a second home run off Oberholtzer in the third inning with a leaping catch above the wall in right field.
"Springer made a great play out there in right to take one away, but I left some balls up," said Oberholtzer, who has pitched only 8 1-3 innings so far.
"I wanted to keep pitching," he said. "I felt pretty good, I had no idea where I was pitch count-wise, but coming out of the game I felt good. I actually didn't think about (the injury) once."
Valencia's third homer came with a man on base in the first, and Smoak led off the second with his fourth homer.
Jason Castro and Springer each hit their third home run of the spring, off Toronto starter Daniel Norris, who left the game optimistic that he will be named to the Blue Jays' starting rotation, perhaps as early as Tuesday.
"It's Christmas," said the 21-year-old left-hander. "We'll see what I get under the tree."
Norris pitched six innings, striking out eight, and giving up four runs on five hits and winning his third straight start.
"I showed 'em that even if I go out there and start rocky, I'm going to finish strong," he said. "I'm not going to pout about giving up a couple homers. We're way past that. It's about growing up and maturing and getting through the fifth and sixth and giving your team a chance to win."
Blue Jays: LHP Brett Cecil, whose spring has been limited to two innings by a sore shoulder, will start the season as the closer, manager John Gibbons said.
Astros: RHP Josh Fields has not pitched since March 23 because of a groin strain. His status for opening day is questionable.
Blue Jays: Norris, who is scheduled to pitch two more innings in Montreal on Saturday, finished the Florida portion of his spring with 29 strikeouts in 24 2-3 innings.
Astros: Oberholtzer threw 70 pitches, including 52 in the first two innings.
HERNANDEZ, THATCHER MAKE STAFF
Hinch informed RHP Roberto Hernandez and LHP Joe Thatcher they would start the season on the 25-man roster. Hernandez will start either the third game against Cleveland, or one of the following two games at Texas.
Blue Jays: Aaron Sachez will start the final spring home game against the Phillies.
Astros: Asher Wojciechowski, who has a 1.08 spring ERA, will make his sixth start against the Braves at Disney.