"I'm sorry, but I just can't stand it anymore," the billionaire Musk wrote in an X post.
"This massive, outrageous, pork-filled Congressional spending bill is a disgusting abomination."
He added: "Shame on those who voted for it: you know you did wrong. You know it."
The House of Representatives last month passed the bill by one vote after the nonpartisan Congressional Budget Office said the measure - which would extend the 2017 tax cuts that were Trump's main legislative accomplishment in his first term - would add $US3.8 trillion ($A5.9 trillion) to the federal government's $US36.2 trillion in debt.
The Senate, also controlled by Trump's Republicans, aims to pass the measure titled the "One Big Beautiful Bill Act" in the next month although senators are expected to revise the House-passed version of the bill.
House Speaker Mike Johnson and Senate Majority Leader John Thune said Musk's calculations were in error.
"It's very disappointing," Johnson told reporters.
"With all due respect, my friend Elon is terribly wrong."
But two House Republicans - Representatives Thomas Massie and Warren Davidson - who opposed the measure went to Musk's social platform X to endorse his message.
"The Big Beautiful Tweet," Davidson said while reposting Musk's words.
Senator Mike Lee, one of at least four Republicans pushing for deeper spending cuts, also rallied to Musk in a tweet that called on party members to use the Trump bill and future spending measures to reduce the deficit.
"We must commit now to doing so, as this is what voters justifiably expect - and indeed deserve - from the GOP Congress," the Utah Republican said on X.
Trump appointed Musk, the world's richest person, to lead a government cost-cutting and efficiency drive, during which he upended several federal agencies but ultimately failed to deliver the massive savings he had sought.
Musk left his formal role in the administration last week as his time as a special government employee with the Department of Government Efficiency came to an end.
The Tesla CEO also criticised the bill in an interview the week before he left, saying it will undermine DOGE's work.
Trump brushed off the criticism.
Musk came out against it even more strongly on Tuesday.
"It will massively increase the already gigantic budget deficit to $2.5 trillion (!!!) and burden America citizens with crushingly unsustainable debt," Musk said on X.
The White House dismissed the most recent attack.
"Look, the president already knows where Elon Musk stood on this bill," spokeswoman Karoline Leavitt said at a White House briefing.
"It doesn't change the president's opinion. This is one big, beautiful bill, and he's sticking to it."
Thune, who aims to pass the bill through his chamber in the next month, said he disagreed with Musk.
"My hope is that as he has an opportunity to further assess what this bill actually does, that he comes to a different conclusion," Thune, of South Dakota, told reporters.
"But nevertheless, I mean, we have a job to do."
