But the Italian club is still not assured of a spot in the knockout stage, reports Efe news.
While Red Star are already eliminated, just 2 points separate Napoli (9) from third-place Liverpool (7).
Paris Saint-Germain, with 8 points, will play the Serbian team in the sixth and final match, but Napoli must travel to Anfield for a showdown with the Reds.
Anxious to erase the memory of a 0-0 draw with Red Star in Belgrade at the start of the campaign, Napoli on Wednesday were dominant from the start Wednesday in front of 40,000 people at San Paolo stadium in Naples.
The hosts continued to press and increased the advantage to 2-0 in the 33rd minute when Dries Mertens scored with an assist from Fabian Ruiz, while only an outstanding intervention by Red Star keeper Milan Borjan denied Kalidou Koulibaly late in the half.
Mertens got his second of the night in the 51st minute, converting a pass from Hamsik to make it 3-0.
Though they conceded a goal six minutes later to Red Star's Ben El Fardou, Napoli were never in any real danger.
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