U.S. Republican rivals Marco Rubio and Ted Cruz ganged up on front-runner Donald Trump at a raucous debate on Thursday in a last-ditch bid to keep the billionaire from winning victories next week that could set him up to clinch the presidential nomination.

The CNN-hosted debate at the University of Houston was the two first-term senators' last, best chance to try to shake up the race for the Republican nomination. The contest is dramatically shifting toward Trump, who is leading in opinion polls in nearly all 11 states set to make their choices on next Tuesday.

RELATED: Trump: Cruz's Canadian birthplace could be 'big problem' for GOP

Rubio and Cruz landed blows on Trump, took some withering fire in return and may wonder why they did not pursue such a strategy in the debates of past weeks and months when former Florida Gov. Jeb Bush, now out of the race, was the lead Trump attacker.

A confident-sounding Trump was unbowed and dismissed the attacks from his center-stage position. He declared Rubio a "choke artist" for a faltering debate in New Hampshire, again labeled Cruz "a liar" and urged his rivals to take their best shot.

"Swing for the fences," he said, wielding a baseball metaphor.

Rubio, who got some momentum with a second-place finish to Trump in South Carolina last Saturday and has picked up some Bush supporters, gave his most aggressive performance to date. The senator from Florida wants to be the last Trump opponent standing and perhaps stretch the contest to the Republican nominating convention in July.

He brought up Trump's four past bankruptcies and his use of imported Polish workers to work at a Florida resort, and pointedly suggested the New Yorker would not be where he is today in the real estate business without a family inheritance.

Without the family money, Rubio said, "You know where Donald Trump would be right now? Selling watches in Manhattan."

RELATED: VIDEO: 'USA Freedom Kids' perform at Trump rally in Florida

Significantly, Rubio sought to raise doubts about the depth of Trump's policy knowledge, a point of attack that Trump's critics in the Republican establishment have been urging candidates to pursue for months.

Rubio pointed out that Trump's sole plan to replace and repeal Democratic President Barack Obama's signature healthcare law is to allow insurance companies to operate across state lines.

When Trump repeated the same point twice, Rubio interrupted.

"Now he's repeating himself," said the senator, who was skewered at a debate in New Hampshire last month for robotically repeating his talking points.

Trump fired back: "I watched him repeat himself five times four weeks ago, and I gotta tell you it was a meltdown. I watched him melt down on the stage like I've never seen anybody."

Cruz, who needs to win his home state of Texas when it votes on Tuesday, also piled on Trump, saying his rival would be a weak Republican opponent to Democratic candidate Hillary Clinton in the Nov. 8 general election because he had donated to the Clinton Foundation founded by her husband, former President Bill Clinton.

Cruz said Hillary Clinton would say to him, "'Gosh, Donald you gave $100,000 to the Clinton Foundation. I even went to your wedding.' ... He can't prosecute the case against Hillary."

RELATED: VIDEO: Even 'Uncle Sam' hates Donald Trump

Trump ridiculed Cruz for his inability to win more than the early voting state of Iowa and taunted him for being behind Trump in opinion polls in Texas. Since a second-place finish in Iowa, Trump has won New Hampshire, South Carolina and Nevada.

"If I can't beat her [Clinton], you're really going to get killed aren't you? ... I know you're embarrassed, but keep fighting," Trump said.

The crossfire was so intense that CNN moderator Wolf Blitzer lost control of the proceedings at times.

Among the other two candidates on the stage, Ohio Gov. John Kasich turned in a positive performance with an optimistic message, hoping Rubio and Cruz will falter and he will end up as the central Trump alternative.

Retired neurosurgeon Ben Carson, flagging in the polls, provided some comic relief. He said that, as president, when considering potential Supreme Court nominees he would look at "the fruit salad of their life" and asked plaintively for more time to talk: "Can someone attack me please?"