The insatiable winger also provided an assist for new recruit Ibrahima Ndiaye, who opened his account following his summer arrival from Swiss side Luzern, as Zamalek went through with a 6-1 aggregate victory over two legs played in Alexandria.
Zizo converted an early penalty but Zamalek were given a brief scare when Leonard Gakwaya levelled the score. However, Senegalese forward Ndiaye got his name on the scoresheet and Zizo netted again before the break to end the match as a contest.
The 26-year-old, the standout performer in Zamalek's triumphant Egyptian Premier League campaign last season, completed his treble with three minutes remaining and substitute Youssef Nabih put the icing on the cake in stoppage time.
Zizo has now contributed to 27 goals in the past 18 games, scoring 16 and creating 11.
Zamalek looked to be cruising to an easy win when Tunisian forward Seifeddine Jaziri was tripped by the keeper after breaking the offside trap as early as the fourth minute, with the referee pointing to the spot.
Zizo sent the keeper the wrong way but Zamalek were surprisingly pegged back after taking the lead, with Flambeau du Centre producing some flowing moves in the final third.
The visitors were rewarded on 25 minutes when a long ball was mis-judged by defender Hossam Abdel-Maguid as Gakawaya raced clear to drill home past advancing goalie Mohamed Awad.
Sensing unexpected danger, Zamalek pushed forward to kill off Flambeau du Centre's hopes. They were guilty of two misses, including a glaring one from central defender Mohamed Abdel-Ghani, who fired over the bar with the goal at his mercy after a defensive lapse.
Ndiaye then eased Zamalek's worries in the 32nd minute, glancing a header home following a trademark inviting corner from Zizo.
Zamalek survived another scare when Abdel-Ghani cleared the ball off the line after keeper Mohamed Awad astonishingly allowed a tame cross to squirm through his legs.
But Zizo put the result beyond doubt five minutes before the break, firing home on the rebound after a low, diagonal cross from Ndiaye caused mayhem in the area.
The second half was a walk of the park for Zamalek as they created chances at will.
They only managed to increase the gap late on though, with Zizo saving the best for the last.
Three minutes from time, he met a fine chipped pass from Ndiaye at the far post with a superb left-foot volley that nestled into the far bottom corner.
Nabih completed the rout three minutes into the additional time with a simple finish after a miscued clearance from defender Amissi Asmani struck the crossbar and fell for the forward to sweep home.
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