For decades, the FARC bankrolled the longest-running conflict in the Americas through the illegal drug trade, kidnapping and extortion.
Battles between the guerrillas, paramilitaries, drug gangs and the army raged in the countryside and there were atrocities committed on all sides.
The conflict took more than 220,000 lives and displaced millions of people. At one stage, the FARC was positioned close to the capital and the state was on the verge of collapse.
Supporters of the peace deal were stunned by the plebiscite result.
"How sad. It seems Colombia has forgotten about the cruelty of war, our deaths, our injured, our mutilated, our victims and the suffering we've all lived through with this war," said Adriana Rivera, 43, a philosophy professor standing tearfully at the hotel of the "yes" campaign.
The vote was a disaster for Santos, who had hoped to turn his focus quickly to other matters including possible talks with the smaller ELN rebel group, a much-needed tax reform and other economic measures to compensate for a drop in oil income.
The government had hoped peace would lead to a boom in investment by commodities investors, in gold mines, oil and agriculture in Latin America's fourth-largest economy.
After Sunday's vote, companies will be rethinking the situation.
Although the "no" camp has broached the idea of fresh talks, the FARC has said no group sits at a negotiating table to agree to jail time.
"Today will be remembered by history as the moment Colombia turned its back on what could have been the end of a war that for more than 50 years devastated millions of lives," said Erika Guevara-Rosas, Americas director for rights group Amnesty International. "Even though it was imperfect, the accord was a sure path to peace and justice."
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