Colorado scored with 9:15 remaining in the second, with Makar putting the puck past Kolosov from almost the same spot as his first goal, but the goal was overturned after Philadelphia successfully challenged for goalie interference.
Makar gave Colorado a 2-0 lead with a power-play goal at 15:08 when his shot from the center of the offensive zone deflected off Flyers defenseman Nick Seeler and past Kolosov.
"He got two, I'm not sure about the third one that was disallowed," Avalanche coach Jared Bednar said. "He got into some good areas on some nice plays from some other players on our team, [Nathan MacKinnon] fed across on the one right into the slot. Just picked the right spots, I felt like tonight, to get up in the rush and join, especially on the entries into the [offensive] zone. In the [offensive] zone play he was pretty active. He found himself in the slot two or three times, all alone, and he didn't make any mistakes on those."
Flyers forward Travis Konecny shouldered the blame for Makar's first goal.
"Bad read, I'm puck-watching," he said. "And it's frustrating to look at the end of the game and it's a one-goal game."
Mittelstadt made it 3-0 at 8:34 of the third period, scoring off the rebound of a Jonathan Drouin shot.
Tippett made it 3-1 with a shot from the high slot at 11:48. Konecny assisted on the play to extend his point streak to seven games (six goals, seven assists).