Police believe Thursday's quadruple fatality at Chiltern was caused by momentary inattention by a driver.
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A Ron Finemore Transport driver was unable to avoid their Subaru in the northbound lanes and crashed into the car, killing all on board.
Work was still being undertaken to formally identify the victims, who are aged in their 70s, on Friday.
Assistant Commissioner Glenn Weir said the crash had been beyond the control of the truck driver, 30.
The group had travelled from central NSW and stopped at Chiltern during their planned trip to Melbourne.
Assistant Commissioner Weir said the journey had been due to take about seven hours but was tragically cut short.
"They've stopped off in Chiltern, it looks like for a break and coffee and have gone to rejoin the highway at Wenkes Road, and for whatever reason have pulled out in front of a B-double that was travelling north on the Hume Highway," he said.
"A catastrophic collision has occurred and four people have been killed.
"We've interviewed the truck driver.
"He was taken to hospital.
"You can imagine the shock that he's in, guy who went to work, just driving his truck, and has been confronted by something beyond his control that's resulted in him being involved in such a tragic accident."
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Assistant Commissioner Weir said dashcam footage had been provided by the Wodonga-based trucking company.
He said even as an experienced officer, the video was "quite confronting".
The driver had been about an hour into a trip, believed to be to Sydney, following a lengthy break, and was in shock after the crash.
Victoria has had nine double fatalities, three quadruple fatalities and one crash that claimed five lives so far this year.
Police have been struggling to understand what has caused a change in driver behaviour and led to the sharp increase in road trauma.
A significant spike had been recorded in the North East.
Investigators returned to the crash site on Friday morning to take photographs of the scene and make other inquiries.
Assistant Commissioner Weir said while there had been improvements in vehicle technology, and cars were more safe than ever, the impact of a B-double hitting a car at such a speed was not survivable.
"Sometimes the most complex problems have simple solutions, and that's what we struggle with," he said.
"It's quite frustrating.
"It's one of those things that the driver will obviously never forget.
"You just feel so sorry for the driver.
"You struggle to understand how that might impact on him, but I'm sure he'll be well taken care of by the company."
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