The 21-year-old, second at the Dubai Desert Classic a fortnight ago, carried on his good form by reeling off nine birdies to finish on 20-under 193, two ahead of Briton Oliver Fisher (66) at the East London Golf Club.
Richard Bland (64) of Britain, seeking a first tour win at the 319th attempt, was a further two shots back along with South African Thomas Aiken (66) and overnight leader John Hahn of the United States (71).
Birdies at the third, fourth, sixth, seventh and eighth took Grillo to the turn in 31 and he also picked up strokes on the 12th, 13th, 15th and 16th as he recorded the best round of the day.
Fisher, winner of the 2011 Czech Open, stayed in touch after a storming finish that included two birdies and an eagle in his final four holes.
(Reporting by Nick Said, editing by Tony Jimenez)
