Former Bosnian Serb leader Radovan Karadzic will begin his closing statement on Wednesday to the Yugoslav war crimes court, where he is charged with some of the worst atrocities in Europe since World War II.

Accused of genocide, war crimes and crimes against humanity, Karadzic, 69, will have a final chance to convince the judges of his innocence, although a final verdict is not expected before late 2015.

He is accused of being one of the masterminds of ethnic cleansing during Bosnia's brutal 1990s war that claimed more than 100,000 lives and uprooted 2.2 million others.

The outspoken Karadzic faces a total of 11 charges, most notably that of genocide for his alleged role in the 1995 Srebrenica massacre.

Almost 8,000 Muslim men and boys were slaughtered and their bodies dumped in mass graves after Bosnian Serb forces overran the UN-protected enclave in eastern Bosnia in July 1995.

Prosecutors wrapped up their arguments on Tuesday saying life behind bars "would be the only appropriate sentence" for the man once known as the president of the self-proclaimed Bosnian Serb republic.

They said Karadzic, along with late Serbian president Slobodan Milosevic and Bosnian Serb general Ratko Mladic, acted together to "cleanse" Bosnia's Muslims and Croats from Serb-claimed territories after the collapse of Yugoslavia in 1991.

Karadzic is also facing charges over the 44-month-long siege of the Bosnian capital Sarajevo, which ended in November 1995 with some 10,000 people killed.

He has 10 hours to address judges on Wednesday and Thursday in what his lawyer Peter Robinson described as a "milestone" in his client's case.

Milosevic died midway through his own trial in March 2006 and Mladic went on trial in May 2012.

Karadzic was arrested on a Belgrade bus in July 2008 disguised as a faith healer and his trial opened in October the following year.

He was absent at the start, telling judges he had not had adequate time to prepare.

When he finally made his opening statement in March 2010, he told judges the wartime atrocities blamed on Bosnian Serbs were "staged" by their Muslim enemies and that the Srebrenica massacre was a "myth".

Later in his trial he told judges that he "should be rewarded" for doing everything possible to prevent Bosnia's bloody civil war.

In his final trial brief filed this week, Karadzic asked judges to look at mitigating factors should he be sentenced, including personal circumstances and that he did not have prior convictions.

Despite still claiming his innocence, Karadzic also apologised to victims of the crimes during the mitigation statements.