There is no known antidote to the drug, the chief neuroscientist (above) at the hospital in Rennes said.
Of the six men in hospital, three could have permanent brain damage, Gilles Edan added.
Reports that the drug is a cannabis-based painkiller have been denied by the health ministry.
A fifth man is suffering from neurological problems and a sixth man is being monitored but is not in a critical condition, Mr Edan said.
The trial, which involved taking the drug orally and has now been suspended, was conducted by a private laboratory in Rennes.
The experimental drug was manufactured by the Portuguese company Bial.
All those who volunteered for the trial have been recalled and the Paris prosecutor's office has opened an investigation.
Health Minister Marisol Touraine pledged to "get to the bottom... of this tragic accident".
"I was overwhelmed by their distress" she told reporters. "Their lives have been brutally turned upside down".
This is the bitter price of the new medicines we take for granted. Testing such experimental drugs, at the cutting edge of science, can never be completely risk-free.
The safety and effectiveness of these drugs are rigorously tested in animals. The risks are low but there must still be a leap of faith when they are tried in people for the first time.
This trial has been taking place since July without such major events being reported.
Generally in Phase I trials the dose is increased slowly over time, which could be why the side-effects are appearing now.
The hospitalized men started taking the drug regularly on 7 January and began showing severe side-effects three days later.
Three of the volunteers are now facing a lifetime of disability in this "accident of exceptional gravity".
It is a high price to pay, but thousands of people do safely take part in similar trials each year.
The trial was conducted by Biotrial, a French-based company with an international reputation which has carried out thousands of trials since it was set up in 1989.
In a message on its website, the company said that "serious adverse events related to the test drug" had occurred.