Raffaele Sollecito, the young Italian accused with his former girlfriend Amanda Knox of murdering Briton Meredith Kercher in 2007, has appealed to a court to dismiss the "absurd" charges.
Addressing the court in Florence, Mr Sollecito, 29, said he had faced "incredible persecution that makes no logical sense at all to me".
He was found guilty and sent to prison in 2009, then freed on appeal in 2011 before a retrial was ordered this year.
"I've been described as a cold and ruthless killer but none of that is true at all," he said.
"Amanda was the first real love of my life," he told the court.
"We wanted to have a life away from everything to live out our own little fairytale.
"I ask you, humbly, to look at the reality of this whole episode and see the big mistake that's been made."
Ms Knox, now back in her home city of Seattle, has opted not to return to Italy for the trial. She has repeatedly denied killing Ms Kercher.
The trial in Florence has re-opened one of the most sensational murder cases in recent Italian history.
It has also renewed questions about the effectiveness of Italy's justice system given widespread doubts over the handling of the investigation and key pieces of evidence.
Ms Kercher, a 21-year-old Leeds University student, was sharing a house with Ms Knox during a year abroad in the picturesque hill town of Perugia when she was killed.
The attack left her body with 40 stab wounds and a deep slash to the throat.
Prosecutors say she was held down and stabbed after she rejected attempts by Ms Knox, Mr Sollecito and another man, Ivory Coast-born Rudy Guede, to involve her in a sex game.
Guede is the only person still in jail for the murder and many aspects still remain unexplained.
Police investigators said today that a fresh analysis of evidence presented in the original hearing had confirmed physical evidence linking Ms Knox to a kitchen knife presumed to have been used in the murder.
"There is a very strong match between DNA from Amanda Knox and what was found on the sample analysed," a police expert from the RIS forensic investigation service told the court.
Francesco Maresca, a lawyer for the Kercher family, said the evidence confirmed that the knife, which was recovered in Mr Sollecito's apartment, had been in Ms Knox's hands, but defence lawyers said it merely showed that experts believed an initial analysis had been carried out correctly.
"This evidence is nothing at all. It crumbles as soon as you look into it," Giulia Bongiorno, Mr Sollecito's lawyer, told reporters.
She said it was unsurprising that Ms Knox's DNA should have been on the knife given that she had often eaten at his house.
In a memoir published earlier this year, Ms Knox described herself as a naive young woman who was railroaded by Italy's creaking and inefficient justice system.
The defence is expected to respond formally on 16-17 December before a prosecution response in January. A verdict is expected on 10 January.