In an unusually strong attack, a North Korean foreign ministry spokesman said comments by Bush calling North Korea a tyrant during campaigning last week in Wisconin were "malignant slanders and calumnies".
"He is a political imbecile bereft of even elementary morality as a human being and a bad guy," said the spokesman, quoted by the official KCNA news agency.
The spokesman blamed Bush for starting wars in Iraq and elsewhere, and said the United States was trying to topple the legitimate government of North Korea.
"Bush's assumption of office turned a peaceful world into a pandemonium unprecedented in history as it is plagued with a vicious circle of terrorism and war," said the statement.
The spokesman went on to describe Bush as "a tyrant that puts Hitler into the shade" as well as "an idiot, an ignorant, a tyrant and a man-killer."
He said that following Bush's comments, it would be "impossible" to hold working-level discussions to prepare for a new round of multilateral talks on the nuclear issue. The talks bring together the two Koreas, China, Japan, Russia and the United States.
"This made it quite impossible for the DPRK (North Korea) to go to the talks and deprived it of any elementary justification to sit at the negotiating table with the US," he said.
The third and last round of six-nation talks were held in Beijing in June and broke up without progress.
The United States wants North Korea to close down all its nuclear weapons facilities in return for a package of economic and diplomatic rewards.
Washington also said it would give North Korea security guarantees that it would not be attacked. The United States currently has no diplomatic ties with North Korea, which is also on the US list of countries sponsoring terrorism.
North Korea rejected the proposals and said it wanted aid and guarantees before it went ahead with freezing its nuclear programmes.
The stand-off over North Korea's quest for nuclear weapons erupted in October 2002 when the United States accused Pyongyang of operating a nuclear weapons programme based on enriched uranium, violating a 1994 nuclear freeze of its separate plutonium producing programme.
Pyongyang has denied running the uranium-based programme, but has again fired up its once-mothballed plutonium-based programme.
The new North Korean statement came as US and South Korean troops Monday began military exercises to test their response to a possible invasion by North Korea.
The North insists the annual two-week exercise is part of Washington's war preparations to topple the Stalinist regime, while Washington says it is purely defensive.
The two-week operation, called Ulchi Focus Lens, focused on computer simulation drills involving an unspecified number of South Korean troops and 14,500 US troops.