"I may be resigning my seat, but I am not giving up my voice," Franken said in the otherwise-hushed Senate chamber.
Franken quit just a day after new allegations brought the number of women alleging misconduct by him to at least eight.
Yesterday, one woman said he forcibly tried to kiss her in 2006, an accusation he vehemently denied. Hours later, another woman said Franken inappropriately squeezed "a handful of flesh" on her waist while posing for a photo with her in 2009.
Franken is the latest to fall in the national wave of sexual harassment allegations that have brought down powerful men in Hollywood, the media and state capitals across the nation. His announcement followed Tuesday's resignation of Michigan Democratic Rep John Conyers, the longest-serving member of the House.
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Franken, the former comedian who made his name on "Saturday Night Live," had originally sought to weather the allegations, disputing many of the specifics but apologizing to his accusers publicly.
"Others I remember quite differently." Still, he said he could not both cooperate with an investigation and fully carry out his duties to his constituents.
Franken, 66, had gained respect as a serious lawmaker in recent years and had even been mentioned in talk about the 2020 presidential race.