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Two other people are also injured following the crash, which has brought four lanes of traffic on the major freeway to a halt.
Footage from 9News’ helicopter appears to show firefighters, paramedics and police pulling several people from a severely damaged car on the bridge.
Two men believed to be in their 20s were trapped in the car and are in a critical condition, according to Ambulance Victoria.
Police have advised the men are the driver of the car and a passenger.
Another man in his 20s and a man believed to be in his 50s were left with minor injuries.
At least three people appear in the footage to have been placed in handcuffs and put in the back of a police van.
However, Victoria Police has not confirmed any arrests.
The Vinnies truck can be seen on its side across two lanes of the road.
The driver or the truck and the passenger were not injured.
Police have said it is understood the car collided with the truck about 10.35am.
The crash occurred in the outbound lanes on the bridge, where three lanes are closed.
One inbound lane has also been closed.
Traffic delays are quickly mounting along on the busy motorway, with motorists advised to avoid the area and use Geelong Road to get to the M80 Ring Road interchange instead of the West Gate Freeway.