The website of Der Spiegel, the weekly news magazine, cited witnesses as saying that after a fist fight, four men had opened fire on the three others.
Two of them were killed, as was a woman who worked at an adjacent Greek restaurant who was hit by a stray bullet in the stomach.
She died in the arms of her husband while waiting for an ambulance to arrive, media reports said.
Der Spiegel said that the woman was pulled to the ground by one of the injured men before both were shot by one of the perpetrators, who then fled.
The third man was seriously injured and remains in hospital.
Police sealed off the area and began a search for the area, involving some 200 officers, sniffer dogs and a helicopter in the heavily populated Rhine-Main area.
Two men were arrested, while the man in hospital has also been made a suspect, prosecutors in the nearby town of Darmstadt said on Wednesday.
German media has reported that possible motives for the murders include unpaid betting debts, a family feud or a dispute over protection money.