The 25-year-old was introduced for Nathan Redmond immediately after the restart in his first game for the Saints since March 2018.
Goals from Che Adams and Maya Yoshida, in the sixth and 34th minutes respectively, had given the visitors the lead in the Stadion Feijenoord.
Towards the end of the encounter, Boufal finished off a brilliant team move to wrap up the win and help Southampton stretch their unbeaten record in the pre-season to four matches.
Boufal will be hoping to build on the goal when Ralph Hasenhuttl's side conclude their preparation for the 2019-20 season against Koln on August 3.
Southampton will begin their Premier League campaign against Burnley at Turf Moor on August 10.