Sean Abbott picked up 1/30 and wicket-keeper Peter Nevill claimed four dismissals as the Victorians were bowled out for for 199 in their first innings.
The Blues posted 177 in response with Daniel Hughes (30) and Moises Henriques (24) amongst the top scorers for the visitors.
At lunch on day three, Victoria were 6/247 with a lead of 275 runs. You can follow the match live here.
Meanwhile, Sixers stars Mitchell Starc (5/34 and 4/74) and Nathan Lyon (3/80) have played a key role in helping Australia into a commanding position in the first test against South Africa in Durban.
Australia requires just one wicket for victory when play resumes on Monday evening, with the South Africans trailing by 123 runs.
In NSW Premier Cricket, Will Somerville picked up 6/87 in Eastern Suburbs' loss to Parramatta, while Daniel Sams finished with figures of 2/42 in Randwick Petersham's loss to Sydney.