"I have been in prison for three years now and I am innocent. It is very frustrating and it is mentally exhausting and I want the truth to be found," she said, speaking in good Italian with a slight American accent. "There have been many mistakes and many prejudices."
Tearing up half-way through the brief statement, Knox went on to say, "I remember how I was young and how I did not understand anything and the most important thing is that I do not want to stay in prison unjustly for all my life."
Today's hearing, which lasted about two hours, was the seventh hearing in the slow-moving appeal trial, which opened in November.
Knox has been imprisoned in Perugia since she was arrested in 2007 and was sentenced to 26 years in prison December 2009 for the brutal killing of the British exchange student who was found on Nov. 2, 2007 with stab wounds to the neck in her room in the cottage she shared with Knox.
For complete coverage of Amanda Knox, check out "THE AMANDA KNOX STORY: A Murder in Perugia," a new ABC Video Book, on sale everywhere enhanced ebooks are sold. Visit www.abcnews.com/videobooks for more information.
Her then-boyfriend, Raffaele Sollecito, was also sentenced in December to 25 years on the same charges.
Both have denied their guilt and protested their innocence.
Another defendant, Rudy Guede, who said he did not kill Kercher but was in the house at the time, was sentenced earlier and separately for the Kercher murder to a 30-year term that was reduced to 16 years on appeal.
Knox's father, Curt, who was in court today said, "It took a lot of courage for Amanda to get up and make a statement like that. I told her [afterwards] that I was very proud of her."
Knox had made a similarly impassioned and emotional plea for her freedom Dec. 11, 2010 in the second hearing in her appeal.
"I am innocent. Raffaele is innocent," she said at that time. "We did not kill Meredith. ... We are paying with our lives for a crime we did not commit."
Today was to have been a crucial hearing, which was originally scheduled to debate the independent review of contested forensic evidence that lawyers for both Knox and Sollecito argue is unsubstantial.
Two court-appointed forensic experts have been tasked with reviewing the DNA evidence on the 30-centimeter kitchen knife found in Sollecito's house and the bra clasp found in Kercher's room.
Defense lawyers have argued that this forensic evidence should never have been used to convict Knox and Sollecito as the results were so weak.
The debate over the evidence will have to wait, however, because the court-appointed independent forensic experts, who had been asked to file their review by May 9, requested a 40-day extension to complete their work.
At today's hearing, the experts also requested they be allowed to consult documents relating to the identification of the alleged murder weapon -- the knife found in Sollecito's kitchen -- and the testimony of the police who searched Sollecito's house that day.
The court today granted their requests, ruling that these documents be handed over to the experts and that the final report must be submitted to the court by June 30 so that it can be discussed at a July 25 hearing.
Other hearings have been set ahead of that date for June 18 and 27 to hear witnesses sought by the defense.
This includes a man in jail for murder who says he knows Knox and Sollecito are innocent and that he knows the name of Kercher's real killers.
A verdict in this appeal trial is not expected until the fall.
Zachary Nowak contributed to this report from Perugia.