Local media reports said a male and a female died instantly, while another woman was seriously injured in the collision, on the northern coast of Crete, at around 6am local time on Monday.
A fourth person, an 18-year-old man, escaped serious injury.
It is believed all four were travelling in a rented 4x4 when it collided with a stationary motorcycle, while local media speculated that the three casualties might not have been wearing seat belts.
A Foreign Office spokesman said: "We are supporting the families of three British people involved in a car accident in Crete, and are in contact with local authorities."
Malia is a popular destination for young holidaymakers, and is known for its nightlife, its sprawling beach and its easy access to Heraklion airport.